The objective of this program is to investigate the integrated function of respiration and circulation. Interaction between the respiratory and circulatory systems may be mediated through mechanical interdependence, changes in respiratory gas tensions, synthesis and release of chemical mediators, and shifts in body fluids. In order to study these interactions, seven interrelated projects are proposed by investigators with expertise in respiratory and cardiovascular physiology. These investigators are supported by co investigators with expertise in biochemistry, pathology, and immunology. Specific goals of the projects are: To assess the basis for mechanical interdependence between the cardiovascular and pulmonary systems (Project 1 - Permutt); To evaluate the regulation of the bronchial circulation and to determine its effects on airway tone and fluid movements in the lungs (Project 2 - Wagner); To characterize responses of the pulmonary circulation to hypoxia and to study mechanisms of hypoxia pulmonary vasoconstriction (Project 3 - Sylvester); To study the effects of stress on airway and vascular tone (Project 4 - Mitzner); To evaluate local mechanisms for the control of airway and vascular tone (Project 5 - Menkes); To assess neurotransmitter function in the control of ventilation (Project 6 - Fitzgerald). These projects are supported by a technical and consultative core with four components - (i) Machine shop, electronic facility, and animal handling (Mitzner), (ii) Pathology (Dannenberg), (iii) Statistic (Kimball), and (iv) Immunology (Liechtenstein). For the individual projects, a variety of approaches will be utilized and range from measurements of chemical mediators in excised smooth muscle tissue to assessments of temperature in exercising human subjects. Although each project is designed so that it can be carried out independently of the others, shared ideas, space, and equipment facilitate progress in the proposed research. This research should in improved understanding of cardiopulmonary interactions and provide a more sound basis for intervention in the acutely ill patient and for prevention of chronic disease.